Tumor targeted fluorescence guidance for intraoperative margin assessment

Abstract

Disclosed are novel detectable imaging agents that can bind to a novel biomarker for cancer and methods of their use in the resection of a tumor.

1 . An anti-CEACAM6 imaging agent comprising the formula Y-R, wherein Y comprises an anti-CEACAM6 binding moiety and R comprises a first detectable label; wherein the first detectable label “R” comprises any dye that emits fluorescent light that is detectable on a clinical optical NIRF imager. 
     
     
         2 . The anti-CEACAM6 imaging agent of  claim 1 , wherein the dye comprises a near infrared dye selected from the group consisting of IRdye800, AlexaFluor 790, ZW-800, Indocyanine Green, and SO456. 
     
     
         3 . The anti-CEACAM6 imaging agent of  claim 1 , wherein the anti-CEACAM6 binding moiety comprises an antibody or anti-CEACAM6 binding antibody fragment. 
     
     
         4 . The anti-CEACAM6 imaging agent of  claim 3 , wherein the anti-CEACAM6 binding moiety comprises an antibody fragment comprising an scFv, F(ab′)2, scFv-Fc (IgG4), or Fab′ that binds CEACAM6. 
     
     
         5 . The anti-CEACAM6 imaging agent of  claim 1 , further comprising a second detectable label. 
     
     
         6 . The anti-CEACAM6 imaging agent of  claim 5 , wherein the second label is a radiolabel. 
     
     
         7 . The anti-CEACAM6 imaging agent of  claim 1 , wherein the anti-CEACAM6 binding moiety is conjugated to the detectable label via a NHS-ester linkage. 
     
     
         8 . The anti-CEACAM6 imaging agent of  claim 1 , wherein the imaging agent is detectable using real-time molecular fluorescence imaging. 
     
     
         9 . The anti-CEACAM6 imaging agent of  claim 1  for use in imaging breast cancer tissue. 
     
     
         10 . The anti-CEACAM6 imaging agent of  claim 9 , wherein the breast cancer tissue is marginal breast cancer tissue. 
     
     
         11 . The anti-CEACAM6 imaging agent of  claim 9 , wherein the agent is administered for imaging marginal breast cancer tissue following lumpectomy. 
     
     
         12 . The use of A method of performing surgical removal of a tumor in a subject comprising:
 a) administering to a subject the anti-CEACAM6 imaging agent of  claim 1 ; and   b) guiding the surgical removal of the tumor using optical surgical navigation.   
     
     
         13 . The method of  claim 12 , wherein the method further comprises assaying the tumor using the anti-CEACAM6 imaging agent to determine the possibility of surgical removal after step a and prior to step b. 
     
     
         14 . The method of  claim 12 , wherein the method further comprises monitoring the progress of the surgical removal. 
     
     
         15 . The method of  claim 12 , wherein the anti-CEACAM6 imaging agent comprises a second detectable label and wherein the second label is a radiolabel. 
     
     
         16 . The method of  claim 12  wherein the method is performed following lumpectomy. 
     
     
         17 . The method of  claim 12  wherein the method is performed following systemic administration for intraoperative margin assessment.